Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade.

BACKGROUND: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. METHODS: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021). RESULTS: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). CONCLUSION: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

Right lower lung midline herniation as a rare complication in an infant with heart-lung transplantation: A case report.

BACKGROUND: Lung herniation is a rare complication of heart-lung transplantation that can be fatal owing to vascular compromise and airway obstruction. To date, only five cases of lung herniation related to heart-lung transplantation have been reported in the literature; however, to the best of our knowledge, this is the first worldwide report of heart-lung transplantation-related lung herniation in an infant. METHODS: We describe the case of lung herniation as a rare heart-lung transplantation-related complication in an infant. A 12-month-old female baby developed severe bronchopulmonary dysplasia with severe pulmonary hypertension, and she underwent extracorporeal membrane oxygenation for cardiac collapse and lung support. Then, we performed heart-lung transplantation to manage the irreversible deterioration of her lung function. After the heart-lung transplantation, we found the radiological abnormalities persisted on follow-up chest radiographs until the 13th postoperative day diagnosed as lung herniation of the right lower lobe on chest computed tomography. RESULTS: After the relocation of the herniated lung, the clinical condition of the patient improved, and the patient is currently growing without any respiratory symptoms. CONCLUSIONS: In this case report, we emphasize that clinical awareness and high suspicion of this rare complication are needed for early diagnosis and proper treatment to prevent post-transplantation morbidity and mortality related to potential ischemic injury.

Development and Validation of Deep-Learning-Based Sepsis and Septic Shock Early Prediction System (DeepSEPS) Using Real-World ICU Data.

BACKGROUND: Successful sepsis treatment depends on early diagnosis. We aimed to develop and validate a system to predict sepsis and septic shock in real time using deep learning. METHODS: Clinical data were retrospectively collected from electronic medical records (EMRs). Data from 2010 to 2019 were used as development data, and data from 2020 to 2021 were used as validation data. The collected EMRs consisted of eight vital signs, 13 laboratory data points, and three demographic information items. We validated the deep-learning-based sepsis and septic shock early prediction system (DeepSEPS) using the validation datasets and compared our system with other traditional early warning scoring systems, such as the national early warning score, sequential organ failure assessment (SOFA), and quick sequential organ failure assessment. RESULTS: DeepSEPS achieved even higher area under receiver operating characteristic curve (AUROC) values (0.7888 and 0.8494 for sepsis and septic shock, respectively) than SOFA. The prediction performance of traditional scoring systems was enhanced because the early prediction time point was close to the onset time of sepsis; however, the DeepSEPS scoring system consistently outperformed all conventional scoring systems at all time points. Furthermore, at the time of onset of sepsis and septic shock, DeepSEPS showed the highest AUROC (0.9346). CONCLUSIONS: The sepsis and septic shock early warning system developed in this study exhibited a performance that is worth considering when predicting sepsis and septic shock compared to other traditional early warning scoring systems. DeepSEPS showed better performance than existing sepsis prediction programs. This novel real-time system that simultaneously predicts sepsis and septic shock requires further validation.

De novo atypical hemolytic uremic syndrome associated with C3 gene mutation after kidney transplantation: a rare case of life-threatening diffuse alveolar hemorrhage in an adolescent.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) disease entity primarily attributed to genetic or acquired abnormalities in the alternative complement pathway. TMA can manifest in kidney transplant (KT) recipients owing to various factors, resulting in diverse clinical presentations. Given its adverse effects on allograft function and patient prognosis, genetic diagnostic approaches for aHUS are essential. Although rarely associated with diffuse alveolar hemorrhage, only a few mild cases have been reported to date. In this report, we present a case of the patient who experienced recurrent and life-threatening diffuse alveolar hemorrhage shortly after KT accompanied by graft failure. CASE PRESENTATION: An 18-year-old girl who underwent deceased donor KT developed recurrent diffuse alveolar hemorrhage with acute kidney injury, leading to graft failure. Microangiopathic hemolytic anemia, thrombocytopenia, and schistocytes in blood smears suggested the presence of TMA. The patient underwent therapeutic plasma exchange, and clinical condition improved during the procedure. Genetic testing confirmed a heterozygous c.1273C>T mutation in C3 gene, leading to the diagnosis of aHUS. However, after discontinuing the plasma exchange, the patient experienced seizures, recurrent pulmonary hemorrhage, and oliguria with recurring TMA features. The patient subsequently underwent eculizumab treatment, which resulted in complete remission, although hemodialysis was continued after graft nephrectomy. CONCLUSION: In patients presenting with unexplained pulmonary hemorrhage and kidney injury following KT, genetic aHUS should be considered as a potential differential diagnosis for TMA.

Early prediction of need for invasive mechanical ventilation in the neonatal intensive care unit using artificial intelligence and electronic health records: a clinical study.

BACKGROUND: Respiratory support is crucial for newborns with underdeveloped lung. The clinical outcomes of patients depend on the clinician's ability to recognize the status underlying the presented symptoms and signs. With the increasing number of high-risk infants, artificial intelligence (AI) should be considered as a tool for personalized neonatal care. Continuous monitoring of vital signs is essential in cardiorespiratory care. In this study, we developed deep learning (DL) prediction models for rapid and accurate detection of mechanical ventilation requirements in neonates using electronic health records (EHR). METHODS: We utilized data from the neonatal intensive care unit in a single center, collected between March 3, 2012, and March 4, 2022, including 1,394 patient records used for model development, consisting of 505 and 889 patients with and without invasive mechanical ventilation (IMV) support, respectively. The proposed model architecture includes feature embedding using feature-wise fully connected (FC) layers, followed by three bidirectional long short-term memory (LSTM) layers. RESULTS: A mean gestational age (GA) was 36.61 ± 3.25 weeks, and the mean birth weight was 2,734.01 ± 784.98 g. The IMV group had lower GA, birth weight, and longer hospitalization duration than the non-IMV group (P < 0.05). Our proposed model, tested on a dataset from March 4, 2019, to March 4, 2022. The mean AUROC of our proposed model for IMV support prediction performance demonstrated 0.861 (95%CI, 0.853-0.869). It is superior to conventional approaches, such as newborn early warning score systems (NEWS), Random Forest, and eXtreme gradient boosting (XGBoost) with 0.611 (95%CI, 0.600-0.622), 0.837 (95%CI, 0.828-0.845), and 0.0.831 (95%CI, 0.821-0.845), respectively. The highest AUPRC value is shown in the proposed model at 0.327 (95%CI, 0.308-0.347). The proposed model performed more accurate predictions as gestational age decreased. Additionally, the model exhibited the lowest alarm rate while maintaining the same sensitivity level. CONCLUSION: Deep learning approaches can help accurately standardize the prediction of invasive mechanical ventilation for neonatal patients and facilitate advanced neonatal care. The results of predictive, recall, and alarm performances of the proposed model outperformed the other models.

Establishment of a Serum-Free Hepatocyte Cryopreservation Process for the Development of an "Off-the-Shelf" Bioartificial Liver System.

To use hepatocytes immediately when necessary for hepatocyte transplantation and bioartificial liver (BAL) systems, a serum-free cryopreservation protocol ensuring the high survival of hepatocytes and maintenance of their functions should be developed. We established a serum-free protocol for the cryopreservation of primary hepatocytes, hepatocyte spheroids, and hepatocyte spheroid beads in liquid nitrogen. The serum-free cryopreservation solutions showed a significantly higher performance in maintaining enhanced viability and ammonia removal, urea secretion, and the albumin synthesis of hepatocyte spheroids and spheroid beads. The serum-free thawing medium, containing human serum albumin (HSA) and N-acetylcysteine (NAC), was compared with a fetal bovine serum-containing thawing medium for the development of a serum-free thawing medium. Our results show that hepatocyte spheroids and spheroid beads thawed using a serum-free thawing medium containing HSA and NAC exhibited increased hepatocyte viability, ammonia removal, urea secretion, and albumin synthesis compared to those thawed using the serum-containing medium. Finally, we evaluated the liver functions of the cryopreserved BAL system-applied serum-free cryopreservation process compared to the fresh BAL system. The ammonia removal efficiency of the cryopreserved hepatocyte spheroids BAL was lower than or similar to that of the fresh BAL system. Additionally, the urea concentrations in the media of all three BAL systems were not significantly different during BAL system operation. This cryopreserved spheroid-based BAL system using a serum-free process will be a good candidate for the treatment of patients.

Melanin decolorization by lysosome-related extract in Saccharomyces cerevisiae modified to overproduce glutathione peroxidase.

All eukaryotes have lysosomes that contain hydrolytic enzymes, such as protease, that degrade waste materials and cellular fragments. As a cellular organelle, lysosomes function as the digestive system of the cell, serving both to degrade material taken up from outside the cell and to digest obsolete components of the cell itself. In a previous study, melanin compounds were bleached using lysosome-related organelle extract (LOE) in which glutathione peroxidase (GPX) contributed decisively to melanin decolorization. In this study, Saccharomyces cerevisiae was engineered to overproduce GPX, which increases the melanin color reduction activity of LOE. In addition, the peroxidase activity of the recombinant yeast was measured for each compartment. In spite of the modification to overexpress the GPX protein, with the peroxidase activity of the lysosome fraction specifically higher, the overall peroxidase activity of the cells remained constant. The overexpression of GPX2 among the GPX present in S. cerevisiae increased both the melanin-decolorization activity and the peroxidase activity of LOE. These results indicate that the peroxidase activity is related to the melanin decomposition and antioxidant enzymes such as GPX. In an artificial skin tissue test, the LOE extracted from the recombinant yeast was efficient in reducing the melanin. These results confirmed the enzyme's ability to penetrate corneous tissue, and they suggest the possibility of further development as a new whitening cosmetic. KEY POINTS: • Modification of Saccharomyces cerevisiae to overexpress glutathione peroxidase (GPX). • The lysosome fraction of the recombinant strain enhanced the decolorizing function. • The LOE penetrates the skin barrier and works effectively on artificial skin tissue.

What has contributed to the large sex differentials in lifespan variation and life expectancy in South Korea?

To date, research on sex differentials in lifespan variation and life expectancy has mainly been conducted in Western countries and there is a dearth of data from South Korea. This study aimed to further the understanding of mortality transition and life expectancy in South Korea, and the associated trajectories of age-at-death variation, through an analysis of life disparity by gender. Using complete life tables for South Korea for 1970-2015, sex differentials (female-male differences) in life disparity and life expectancy at birth were estimated, and sex differentials in life expectancy were decomposed by age and cause of death. The results showed that sex differentials in life expectancy at birth have not reduced significantly in the last 45 years (1970: 7.1 years; 2015: 6.2 years). Life disparity has reduced more rapidly for females than males, and the difference increased from -0.1 year in 1981 to -1.6 years in 2015. Sex differentials in life expectancy and life disparity in South Korea were higher during 1970-2015 than in several Western countries with high life expectancy. The elderly age group (60 and above) contributed 50% of the total sex difference in life expectancy at birth in 1970, and this increased to 70% in 2015. The contribution of the age group 15-59 years reduced significantly over the period. Decomposition of life expectancy at birth by cause revealed that diseases of the circulatory system (2.2 years), followed by external causes (1.3 years), were the most important causes of the sex differences in life expectancy at birth in 1983, and in 2015 neoplasms (2.2 years) and external causes (1.1 years) explained half of the total sex differences. There has been a significant shift in the age-specific pattern of the contribution towards each cause of death. Overall, sex differentials in life disparity and life expectancy at birth have remained significant in South Korea in the last 45 years.

YPT7's deletion regulates yeast vacuoles' activity.

The yeast vacuole is functionally corresponding to vacuoles in eukaryote cells, it consists of a fusion protein that assists in the fusion of vacuoles and plays an important role in many processes. In addition, chemicals such as NH4Cl can reduce the size of vacuoles but as a side effect that also inhibits vacuoles making them inactive. In this study, to develop pre-treatments for extending the life of cut flowers, we constructed recombinant yeast using the fusion protein YPT7 and confirmed the activity of down-sized vacuoles. All the vacuoles of the recombinant yeast except vacuoles from recombinant yeast (MBTL-MYH-3) were found to be small vacuoles than mock (MBTL-MYH-0) and YPT7 overexpression model (MBTL-MYH-1). To confirm their activity, we conducted a test for antimicrobial activity. The results showed the other vacuoles of recombinant yeast had lower antimicrobial activity than the mock control, most of them showed about 60 % to 80 % of the antimicrobial activity. However, MBTL-MYH-3, whose vacuole did not change its size, showed antimicrobial activity lower than 40 %. Therefore, the cut flowers are better able to absorb smaller vacuoles after using the fusion protein YPT7. We expect that absorbing vacuoles more effective to senescence of cut flower than vacuolar enzymes.

Metabolomic study of polyamines in rat urine following intraperitoneal injection of γ-hydroxybutyric acid.

INTRODUCTION: Recently, illegal abuse of γ-hydroxybutyric acid (GHB) has increased in drug-facilitated crimes, but the determination of GHB exposure and intoxication is difficult due to rapid metabolism of GHB. Its biochemical mechanism has not been completely investigated. And a metabolomic study by polyamine profile and pattern analyses was not performed in rat urine following intraperitoneal injection with GHB. OBJECTIVES: Urinary polyamine (PA) profiling by gas chromatography-tandem mass spectrometry was performed to monitor an altered PA according to GHB administration. METHODS: Polyamine profiling analysis by gas chromatography-mass spectrometry combined with star pattern recognition analysis was performed in this study. The multivariate statistical analysis was used to evaluate discrimination among control and GHB administration groups. RESULTS: Six polyamines were determined in control, single and multiple GHB administration groups. Star pattern showed distorted hexagonal shapes with characteristic and readily distinguishable patterns for each group. N1-Acetylspermine (p < 0.001), putrescine (p < 0.006), N1-acetylspermidine (p < 0.009), and spermine (p < 0.027) were significantly increased in single administration group but were significantly lower in the multiple administration group than in the control group. N1-Acetylspermine was the main polyamine for discrimination among control, single and multiple administration groups. Spermine showed similar levels in single and multiple administration groups. CONCLUSIONS: The polyamine metabolic pattern was monitored in GHB administration groups. N1-Acetylspermine and spermine were evaluated as potential biomarkers of GHB exposure and addiction.

Subglottic stenosis in children: Our experience at a pediatric tertiary center for 8 years in South Korea.

OBJECTIVE: The incidence of SGS has been reported to be less than 8% after endotracheal intubation. Therefore there is an increasing trend in the number of patients with acute acquired SGS due to mechanical ventilation in the intensive care unit. However, there have been no reports describing the treatment of SGS in children in South Korea. The objective of this study was to evaluate the management and outcomes of children with SGS at a pediatric tertiary center in South Korea over an 8-year period. METHODS: All patients underwent microlaryngobronchoscopy (MLB) with bougination, incision using cold knife or laser and balloon dilatation. Data on age, sex, grade of SGS, number of management interventions, tracheostomy, comorbidities, mean follow-up period, complications, and outcome were reviewed from patient medical charts. RESULTS: Twenty patients (13 [65%] males, 7 [35%] females; mean [±SD] age at the diagnostic procedure 15.26 ±â€¯22.54 months) underwent MLB between March 2009 and December 2017. According to the Myer-Cotton scale, twelve of the 20 (60%) patients had grade III SGS, 7 (35%) had grade II and 1 (5%) had grade 1; there were no patients with grade IV SGS. Nine (45%) patients were diagnosed with acute SGS, and 11 (55%) with chronic SGS. Patients with SGS underwent MLB with interventions (mean 2.41 ±â€¯2.23 per patient). Tracheostomy was performed in 13 of 20 (65%) patients, 2 of 9 (22.2%) with acute SGS, and 11 of 11 (100%) with chronic SGS. Two of 13 (15.3%) patients underwent successful decannulation. One of 2 (50%) patients with acute SGS underwent successful decannulation. Seven of 9 (77.7%) patients with acute SGS underwent MLB only without tracheostomy. CONCLUSIONS: In patients with acute acquired SGS, the outcome was good due to the lower rate of tracheostomy and higher decannulation rate. Therefore, it is recommended that MLB with balloon laryngoplasty be performed at the earliest in patients with acute acquired SGS.

Effect of the combination of Mendelsohn maneuver and effortful swallowing on aspiration in patients with dysphagia after stroke.

[Purpose] This study investigated the effect of a combined method incorporating the Mendelsohn maneuver and effortful swallowing on aspiration in patients with dysphagia after stroke. [Subjects and Methods] Three patients with dysphagia were recruited. All patients were treated with a combined method consisting of the Mendelsohn maneuver and effortful swallowing. The intervention period was total 20 sessions. Evaluation was based on videofluoroscopic swallowing study and the degree of aspiration was assessed using penetration-aspiration scale. [Results] Before and after intervention, all participants showed a decrease in aspiration with liquid type and semisolid type food. [Conclusion] This study confirms that the combined method of the Mendelsohn maneuver and effortful swallowing has a positive effect on aspiration in patients with dysphagia after stroke.

Effects of jaw opening exercise on aspiration in stroke patients with dysphagia: a pilot study.

[Purpose] The purpose of this study was to investigate the effect of jaw opening exercise (JOE) on aspiration in patients with dysphagia after stroke. [Subjects and Methods] Three subjects were recruited. Isometric and isotonic JOE were performed using a rubber ball, 5 days a week for 4 weeks. Aspiration was evaluated using the penetration-a spiration scale (PAS) based on a videofluoroscopic swallowing study. [Results] All subjects showed a score reduction of at least 1 point and a maximum reduction of 2 points in the PAS in the liquid type. [Conclusion] This study confirmed that JOE can be used to reduce aspiration in patients with dysphagia after stroke.

Sesquiterpene derivatives from marine sponge Smenospongia cerebriformis and their anti-inflammatory activity.

Using various chromatographic methods, five new sesquiterpene derivatives named smenohaimiens A-E (1-5) and five known, 19-hydroxy-polyfibrospongol B (6), ilimaquinone (7), dictyoceratin C (8), polyfibrospongol A (9), and polyfibrospongol B (10) were isolated from the marine sponge Smenospongia cerebriformis Duchassaing & Michelotti, 1864. Their structures were assigned by 1D, 2D NMR spectroscopic analysis, HR ESI MS, and calculations of the electron circular dichroism spectra. All compounds were evaluated for the inhibitory activity against NO production in lipopolysaccharide-stimulated in BV2 microglia cells. As the results, compound 7 significantly inhibited NO production with the IC50 value of 10.40±1.28µM. The remaining compounds showed moderate inhibitory NO production activities with IC50 values ranging from 24.37 to 30.43µM.

Effect of germinated grain flours on physicochemical characteristics of rice cakes, Seolgitteok.

Minor grains and their germinated shoots such as buckwheat, Job's tears, and mungbean have diverse bioactive functionalities. In this study, the flours of grains and germinated grains were added to Korean rice cakes, known as Seolgitteok, and the effects on properties such as starch gelatinization and retrogradation were examined. The dietary fiber content, blue value index, amylogram, texture properties and sensory evaluation of Seolgitteok were also investigated. Rice flour amylogram results showed that addition of buckwheat, germinated Job's tears, and mungbean decreased starch setback, and that addition of buckwheat decreased consistency, which are related to slowed retrogradation. Buckwheat, especially when germinated, delayed starch retrogradation, which is one of the main drawbacks of rice cakes. Seolgitteok with added germinated buckwheat possessed preferable sensory qualities.

Coniferaldehyde inhibits LPS-induced apoptosis through the PKC α/ß II/Nrf-2/HO-1 dependent pathway in RAW264.7 macrophage cells.

Coniferaldehyde (CA) exerts anti-inflammatory properties by inducing heme oxygenase-1 (HO-1). To define the regulation mechanism by which CA induces a cytoprotective function and HO-1 expression, the up-stream regulations involved in the activation of nuclear transcription factor-erythroid 2-related factor (Nrf)-2/HO-1 pathway were investigated. CA dramatically increased the Nrf-2 nuclear translocation and HO-1 expression. Lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and cell death were down-regulated by CA, which were reversed by inhibition of HO-1 activity. Furthermore, CA specifically enhanced the phosphorylation of protein kinase C (PKC) α/ß II. Selective inhibition of PKC α/ß II using Go6976 or siRNA abolished the CA-induced Nrf-2/HO-1 signaling, and consequently suppressed the cytoprotective activity of CA on the LPS-induced cell death. Together, our results elucidate the regulatory mechanism of PKC α/ß II as the upstream molecule of Nrf-2 required for HO-1 expression during CA-induced anti-inflammatory cytoprotective function in LPS stimulated macrophages.

Up-regulation of the receptor for advanced glycation end products in the skin biopsy specimens of patients with severe diabetic neuropathy.

BACKGROUND AND PURPOSE: The receptor for advanced glycation end products (RAGE) may contribute to the development of diabetic neuropathy. To assess its relevance in humans, this study examined the expression of RAGE in the skin biopsy samples of patients with diabetes mellitus, and investigated its correlation with intraepidermal nerve-fiber density (IENFD) and clinical measures of neuropathy severity. METHODS: Forty-four patients who either had type 2 diabetes or were prediabetes underwent clinical evaluation and a 3-mm skin punch biopsy. The clinical severity of their neuropathy was assessed using the Michigan Diabetic Neuropathy Score. IENFD was measured along with immunohistochemical staining for RAGE in 29 skin biopsy samples. The expression of RAGE was also quantified by real-time reverse-transcription PCR in the remaining 15 patients. RESULTS: RAGE was localized mostly in the dermal and subcutaneous vascular endothelia. The staining was more intense in patients with a lower IENFD (p=0.004). The quantity of RAGE mRNA was significantly higher in patients with severe neuropathy than in those with no or mild neuropathy (p=0.003). The up-regulation of RAGE was related to dyslipidemia and diabetic nephropathy. There was a trend toward decreased sural nerve action-potential amplitude and slowed peroneal motor-nerve conduction with increasing RAGE expression. CONCLUSIONS: The findings of this study demonstrate up-regulation of RAGE in skin biopsy samples from patients with diabetic neuropathy, supporting a pathogenic role of RAGE in the development of diabetic neuropathy.

Red meat consumption is associated with an increased overall cancer risk: a prospective cohort study in Korea.

Cancer is a leading cause of death, and the dietary pattern in Korea is changing rapidly from a traditional Korean diet to a Westernised diet. In the present study, we investigated the effects of dietary factors on cancer risk with a prospective cohort study. Among 26,815 individuals who participated in cancer screening examinations from September 2004 to December 2008, 8024 subjects who completed a self-administered questionnaire concerning demographic and lifestyle factors, and a 3 d food record were selected. As of September 2013, 387 cancer cases were identified from the National Cancer Registry System, and the remaining individuals were included in the control group. The hazard ratio (HR) of cancer for the subjects older than or equal to 50 years of age was higher (HR 1.80, 95% CI 1.41, 2.31; P< 0.0001) than that for the other subjects. Red meat consumption, Na intake and obesity (BMI ≥ 25 kg/m²) were positively associated with overall cancer incidence in men (HR 1.41, 95% CI 1.02, 1.94; P= 0.0382), gastric cancer (HR 2.34, 95% CI 1.06, 5.19; P= 0.0365) and thyroid cancer (HR 1.56, 95% CI 1.05, 2.31; P= 0.0270), respectively. Participants who had at least three dietary risk factors among the high intakes of red meat and Na, low intakes of vegetables and fruits, and obesity suggested by the World Cancer Research Fund/American Institute for Cancer Research at baseline tended to have a higher risk of cancer than the others (HR 1.26, 95% CI 0.99, 1.60; P= 0.0653). In summary, high intakes of red meat and Na were significant risk factors of cancer among Koreans.

Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation.

Stromal-derived follicular dendritic cells (FDCs) are a major reservoir for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate. A long-standing question is how FDCs retain antigen in its native form for extended periods and how they display it to specific B cells. Here we found that FDCs acquired complement-coated immune complexes (ICs) from noncognate B cells via complement receptors 1 and 2 (CD35 and CD21, respectively) and rapidly internalized them by an actin-dependent pathway. ICs were retained intact within a nondegradative cycling compartment and were displayed periodically on the cell surface where they were accessible to antigen-specific B cells. This would explain how antigens are protected from damage and retained over long periods of time, while remaining accessible for B cells.

Cochlin produced by follicular dendritic cells promotes antibacterial innate immunity.

Cochlin, an extracellular matrix protein, shares homologies with the Factor C, a serine protease found in horseshoe crabs, which is critical for antibacterial responses. Mutations in the COCH gene are responsible for human DFNA9 syndrome, a disorder characterized by neurodegeneration of the inner ear that leads to hearing loss and vestibular impairments. The physiological function of cochlin, however, is unknown. Here, we report that cochlin is specifically expressed by follicular dendritic cells and selectively localized in the fine extracellular network of conduits in the spleen and lymph nodes. During inflammation, cochlin was cleaved by aggrecanases and secreted into blood circulation. In models of lung infection with Pseudomonas aeruginosa and Staphylococcus aureus, Coch(-/-) mice show reduced survival linked to defects in local cytokine production, recruitment of immune effector cells, and bacterial clearance. By producing cochlin, FDCs thus contribute to the innate immune response in defense against bacteria.